Hepatitis C screening in Lithuania: first-year results and scenarios for achieving WHO elimination targets.

BACKGROUND: The World Health Organization (WHO) has outlined a set of targets to achieve eliminating hepatitis C by 2030. In May 2022, Lithuanian health authorities initiated a hepatitis C virus (HCV) screening program to start working towards elimination. In the program, bonus was given to general practitioners (GPs) to promote and conduct anti-HCV tests for two situations: (1) one time testing for individuals born in 1945-1994 and (2) annual HCV testing for persons who inject drugs or are living with human immunodeficiency virus (HIV) regardless of age. This study aimed to model the current viral hepatitis C epidemiological status in Lithuania and to outline the requirements for WHO elimination targets using the first-year HCV screening results. METHODS: Individuals were invited to participate in the anti-HCV screening by GPs during routine visits. Patients who tested positive were then referred to a gastroenterologist or infectious disease doctor for further confirmatory testing. If a patient received a positive RNA test and a fibrosis staging result of ≥ F2, the doctor prescribed direct-acting antivirals. Information on the patients screened, diagnosed, and treated was obtained from the National Health Insurance Fund. The Markov disease progression model, developed by the CDA Foundation, was used to evaluate the screening program results and HCV elimination progress in Lithuania. RESULTS: Between May 2022 and April 2023, 790,070 individuals underwent anti-HCV testing, with 11,943 individuals (1.5%) receiving positive results. Anti-HCV seroprevalence was found to be higher among males than females, 1.9% and 1.2%, respectively. Within the risk population tested, 2087 (31.1%) seropositive individuals were identified. When comparing the screening program results to WHO elimination targets through modelling, 2180 patients still need to be treated annually until 2030, along with expanding fibrosis restrictions. If an elimination approach was implemented, 1000 new infections would be prevented, while saving 150 lives and averting 90 decompensated cirrhosis cases and 110 hepatocellular carcinoma cases. CONCLUSIONS: During the first year of the Lithuanian screening program, GPs were able to screen 44% of the target population. However, the country will not meet elimination targets as it currently stands without increasing treatment levels and lifting fibrosis restrictions.

Antibiotic resistance in patients with liver cirrhosis: Prevalence and current approach to tackle.

Regardless of etiology, complications with bacterial infection in patients with cirrhosis are reported in the range of 25%-46% according to the most recent data. Due to frequent episodes of bacterial infection and repetitive antibiotic treatment, most often with broad-spectrum gram negative coverage, patients with cirrhosis are at increased risk of encountering multidrug resistant bacteria, and this raises concern. In such patients, extended-spectrum beta-lactamase and AmpC-producing Enterobacterales, methicillin- or vancomycin-resistant Staphylococcus aureus, vancomycin-resistant Enterococci, carbapenem-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii, all of which are difficult to treat, are the most common. That is why novel approaches to the prophylaxis and treatment of bacterial infections to avoid antibiotic resistance have recently been developed. At the same time, our knowledge of resistance mechanisms is constantly updated. This review summarizes the current situation regarding the burden of antibiotic resistance, including the prevalence and mechanisms of intrinsic and acquired resistance in bacterial species that most frequently cause complications in patients with liver cirrhosis and recent developments on how to deal with multidrug resistant bacteria.

Menstrual cycle abnormalities in women with inflammatory bowel disease and effects of biological therapy on gynecological pathology.

Inflammatory bowel disease (IBD) is a chronic condition that affects young individuals in their reproductive years. It may have long-term implications on their reproductive, sexual, and mental health. IBD has been related to menstrual abnormalities. Furthermore, the administration of biological therapy can also result in gynecological issues in addition to the disease itself. The purpose of this review was to present potential menstrual cycle problems in patients with IBD, as well as the impact of adalimumab and other anti-tumor necrosis factor medications on gynecological pathology.

Effects of COVID-19 on the liver: The experience of a single center.

BACKGROUND: The coronavirus disease 2019 (COVID-19) was perhaps the most severe global health crisis in living memory. Alongside respiratory symptoms, elevated liver enzymes, abnormal liver function, and even acute liver failure were reported in patients suffering from severe acute respiratory disease coronavirus 2 pneumonia. However, the precise triggers of these forms of liver damage and how they affect the course and outcomes of COVID-19 itself remain unclear. AIM: To analyze the impact of liver enzyme abnormalities on the severity and outcomes of COVID-19 in hospitalized patients. METHODS: In this study, 684 depersonalized medical records from patients hospitalized with COVID-19 during the 2020-2021 period were analyzed. COVID-19 was diagnosed according to the guidelines of the National Institutes of Health (2021). Patients were assigned to two groups: those with elevated liver enzymes (Group 1: 603 patients), where at least one out of four liver enzymes were elevated (following the norm of hospital laboratory tests: alanine aminotransferase (ALT) ≥ 40, aspartate aminotransferase (AST) ≥ 40, gamma-glutamyl transferase ≥ 36, or alkaline phosphatase ≥ 150) at any point of hospitalization, from admission to discharge; and the control group (Group 2: 81 patients), with normal liver enzymes during hospitalization. COVID-19 severity was assessed according to the interim World Health Organization guidance (2022). Data on viral pneumonia complications, laboratory tests, and underlying diseases were also collected and analyzed. RESULTS: In total, 603 (88.2%) patients produced abnormal liver test results. ALT and AST levels were elevated by a factor of less than 3 in 54.9% and 74.8% of cases with increased enzyme levels, respectively. Patients in Group 1 had almost double the chance of bacterial viral pneumonia complications [odds ratio (OR) = 1.73, P = 0.0217], required oxygen supply more often, and displayed higher biochemical inflammation indices than those in Group 2. No differences in other COVID-19 complications or underlying diseases were observed between groups. Preexisting hepatitis of a different etiology was rarely documented (in only 3.5% of patients), and had no impact on the severity of COVID-19. Only 5 (0.73%) patients experienced acute liver failure, 4 of whom died. Overall, the majority of the deceased patients (17 out of 20) had elevated liver enzymes, and most were male. All deceased patients had at least one underlying disease or combination thereof, and the deceased suffered significantly more often from heart diseases, hypertension, and urinary tract infections than those who made recoveries. Alongside male gender (OR = 1.72, P = 0.0161) and older age (OR = 1.02, P = 0.0234), diabetes (OR = 3.22, P = 0.0016) and hyperlipidemia (OR = 2.67, P = 0.0238), but not obesity, were confirmed as independent factors associated with more a severe COVID-19 infection in our cohort. CONCLUSION: In our study, the presence of liver impairment allows us to predict a more severe inflammation with a higher risk of bacterial complication and worse outcomes of COVID-19. Therefore, patients with severe disease forms should have their liver tests monitored regularly and their results should be considered when selecting treatment to avoid further liver damage or even insufficiency.

Gut microbiota contribution to hepatocellular carcinoma manifestation in non-alcoholic steatohepatitis.

Recently, the gut microbiota has been recognized as an obvious active player in addition to liver steatosis/steatohepatitis in the pathophysiological mechanisms of the development of hepatocellular carcinoma (HCC), even in the absence of cirrhosis. Evidence from clinical and experimental studies shows the association of specific changes in the gut microbiome and the direct contribution to maintaining liver inflammation and/or cancerogenesis in nonalcoholic fatty liver disease-induced HCC. The composition of the gut microbiota differs significantly in obese and lean individuals, especially in the abundance of pro-inflammatory lipopolysaccharide-producing phyla, and, after establishing steatohepatitis, it undergoes minor changes during the progression of the disease toward advanced fibrosis. Experimental studies proved that the microbiota of obese subjects can induce steatohepatitis in normally fed mice. On the contrary, the transplantation of healthy microbiota to obese mice relieves steatosis. However, further studies are needed to confirm these findings and the mechanisms involved. In this review, we have evaluated well-documented clinical and experimental research on the role of the gut microbiota in the manifestation and promotion of HCC in nonalcoholic steatohepatitis (NASH). Furthermore, a literature review of microbiota alterations and consequences of dysbiosis for the promotion of NASH-induced HCC was performed, and the advantages and limitations of the microbiota as an early marker of the diagnosis of HCC were discussed.

Management of Flood syndrome: What can we do better?

Approximately 20% of cirrhotic patients with ascites develop umbilical herniation. These patients usually suffer from multisystemic complications of cirrhosis, have a significantly higher risk of infection, and require accurate surveillance- especially in the context of the coronavirus disease 2019 pandemic. The rupture of an umbilical hernia, is an uncommon, life-threatening complication of large-volume ascites and end-stage liver disease resulting in spontaneous paracentesis, also known as Flood syndrome. Flood syndrome remains a challenging condition for clinicians, as recommendations for its management are lacking, and the available evidence for the best treatment approach remains controversial. In this paper, four key questions are addressed regarding the management and prevention of Flood syndrome: (1) Which is the best treatment approach-conservative treatment or urgent surgery? (2) How can we establish the individual risk for herniation and possible hernia rupture in cirrhotic patients? (3) How can we prevent umbilical hernia ruptures? And (4) How can we manage these patients in the conditions created by the coronavirus disease 2019 pandemic?

Complicated course of biliary inflammatory myofibroblastic tumor mimicking hilar cholangiocarcinoma: A case report and literature review.

BACKGROUND: The inflammatory myofibroblastic tumor (IMT) is a rare, idiopathic, usually benign, mass-forming disease with myofibroblastic proliferation and a varying amount of inflammatory cells. Although it can affect various organs, the biliary tract is a rare localization of primary IMT, clinically, endoscopically and radiologically imitating cholangiocarcinoma. The treatment options are based only on clinical practice experience. CASE SUMMARY: A 70-year-old woman was referred to our center due to progressive fatigue, weight loss, abdominal pain, night sweats, and elevated liver enzymes. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed proximal common hepatic duct and hilar biliary strictures extending bilaterally to lobular bile ducts. Although initial clinical, endoscopic and radiological signs were typical for hilar cholangiocarcinoma, histological examination showed no signs of malignancy. In total, 8 biopsies using different approaches were performed (several biopsies from dominant stricture during ERCP and direct cholangioscopy; ultrasound-guided liver biopsy; diagnostic laparoscopy with liver and lymph node biopsies). Histological examination revealed signs of IMT, and the final diagnosis of biliary IMT was stated. Although IMT is usually a benign disease, in our case, it was complicated. All pharmacological treatment measures were ineffective. The patient still needs permanent stenting, suffers from recurrent infections and mechanical jaundice. Despite that, the patient already survived 24 mo. CONCLUSION: IMT presenting with hilar biliary strictures is a unique diagnostic and clinical challenge as it is indistinguishable from cholangiocarcinoma, and there are no evidence-based treatment options. Our goal is to increase the understanding of this rare disease and its possible course.

Paraneoplastic Phenomena of Disseminated Intravascular Coagulopathy in Hepatic Angiosarcoma - Rare, Challenging and Fatal. Case Report and Literature Review.

Background: Hepatic angiosarcoma is an uncommon, malignant, primary liver tumor, comprising 2% of liver cancers and accounting for < 1% of all sarcomas. Patients usually present with nonspecific symptoms, such as fatigue, weight loss, right upper quadrant pain, anemia, which leads to late diagnosis of an advanced stage tumor. The median life expectancy after the diagnosis of hepatic angiosarcoma is about 6 months, with only 3% of patients surviving more than 2 years. Liver failure and hemoperitoneum are the leading causes of death in patients with liver angiosarcoma. In rarer cases, it might cause paraneoplastic syndromes such as disseminated intravascular coagulopathy. The treatment of angiosarcomas is complicated as there are no established and effective treatment guidelines due to the tumor's low frequency and aggressive nature. Case summary: We present the case of a 68-year old woman who was admitted to the hospital due to fatigue and severe anemia (hemoglobin 65 g/l). Laboratory results also revealed high-grade thrombocytopenia (8 × 109/l). The abdominal ultrasound and computed tomography scan showed multiple lesions throughout the liver, spleen and kidneys. After the histological examination of the liver biopsy, the patient was diagnosed with hepatic angiosarcoma. The treatment with first-line chemotherapy (doxorubicin) was initiated despite ongoing paraneoplastic syndrome - disseminative intravascular coagulopathy. However, the disease was terminal, and the patient died 2 months since diagnosed. Conclusions: Hepatic angiosarcoma is a rare and terminal tumor. Therefore, knowledge about its manifestations and effective treatment methods is lacking. Disseminative intravascular coagulopathy is a unique clinical characteristic of angiosarcoma seen in a subset of patients.

Multi-organ IgG4-related disease continues to mislead clinicians: A case report and literature review.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a multisystemic mass forming immune-mediated disease that affects almost every organ and is a diagnostic challenge for every clinician. There is a lack of adequate epidemiological data worldwide, and evidence-based treatment recommendations are not yet established. We report the first case of IgG4-RD from Lithuania and the Baltic Sea region presented with thyroiditis, orbital myositis, orbitopathy, uveitis, scleritis, sialadenitis, autoimmune pancreatitis and prostatitis. CASE SUMMARY: A 54-year-old Caucasian male was admitted to our tertiary Centre complaining of severe weight loss, diarrhoea, abdominal pain, salivary gland swelling, sicca symptoms and diplopia. On examination, bilateral palpable masses in the projection of major salivary glands, severe protrusion of the left eyeball and cachexia were noted. The patient was previously diagnosed with autoimmune thyroiditis and endocrine ophthalmopathy. The magnetic resonance imaging (MRI) of the head revealed enlarged extraocular muscles indicating orbital myositis. The biopsy from the salivary gland mass indicated sialadenitis. Abdominal MRI showed signs of autoimmune pancreatitis, and a serological test revealed the elevated serum IgG4 concentration. The patient was then diagnosed with IgG4-RD and successfully treated with prednisolone. There was a significant clinical, serological and radiological improvement after one month of treatment and no signs of relapse within twenty months. However, it took almost 18 years and the efforts of eight different medical specialists to establish the correct diagnosis. CONCLUSION: A comprehensive approach to the patient is essential to improving the recognition of rare immune system conditions, such as IgG4-RD.

Mucosa-associated lymphoid tissue lymphoma simulating Crohn's disease: A case report.

BACKGROUND: Differential diagnosis between extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and inflammatory bowel disease is mainly based on histopathologic evaluation of intestinal biopsies, although there is no single definitive diagnostic investigation and that circumstance can lead to misdiagnosis in particular cases. Herein we present a rare, ulcerative form of marginal zone lymphoma which mimics the Crohn's disease (CD) of upper digestive tract. CASE SUMMARY: A 50-year-old man was presented with recurrent episodes of malaise and melena also weight loss. Enteroscopy of the small bowel demonstrated an ulcer in the jejunum. Microscopically, biopsies showed lymphoplasmacytic infiltrate. Diagnosis of CD was made. Primary treatment consisted of prednisone and azathioprine and was followed by azathioprine 100 mg per day with good clinical response in the following 2 years until relapse. At this time the results of endoscopic biopsies derived from proximal wall of stomach revealed Helicobacter pylori-negative marginal zone lymphoma of the gastric fundus. Immunophenotyping confirmed atypical CD20-positive cell population. Based on these biopsies, marginal zone lymphoma of mucosa-associated lymphoid tissue was diagnosed. Unfortunately, the contact with the patient was lost until one year later he was hospitalized with nausea, vomiting and severe pain because of gastrointestinal perforation. Four months later after laparotomy, the patient was treated with a course of chemotherapy. Complete remission was observed following 6 cycles of treatment. CONCLUSION: This case report highlights the clinical relevance of knowledge and awareness of marginal zone lymphoma simulating CD.

Liver cirrhosis and left ventricle diastolic dysfunction: Systematic review.

BACKGROUND: Liver cirrhosis is a chronic hepatic disease which is associated with cardiovascular abnormalities. Hyperdynamic circulation in liver cirrhosis causes functional and structural cardiac alterations. The prevalence of left ventricle diastolic dysfunction (LVDD) in cirrhotic patients ranges from 25.7% to as high as 81.4% as reported in different studies. In several studies the severity of diastolic dysfunction (DD) correlated with a degree of liver failure and the rate of dysfunction was higher in patients with decompensated cirrhosis compared with compensated. Future directions of comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients. AIM: To clarify the correlation between the severity of liver cirrhosis and left ventricle diastolic dysfunction in the existing literature. METHODS: Through January and February of 2019 at Vilnius University we conducted a systematic review of the global existing literature on the prevalence of left ventricle diastolic dysfunction in patients with liver cirrhosis. We searched for articles in PubMed, Medline and Web of science databases. Articles were selected by using adequate inclusion and exclusion criteria. Our interest was the outcome of likely correlation between the severity of cirrhosis [evaluated by Child-Pugh classes, Model For End-Stage Liver Disease (MELD) scores] and left ventricle diastolic dysfunction [classified according to American Society of Echocardiography (ASE) guidelines (2009, 2016)], as well as relative risk of dysfunction in cirrhotic patients. Subgroup analyses were performed to evaluate the ratio and grades of left ventricle diastolic dysfunction with respect to cirrhosis severity. RESULTS: A total of 1149 articles and abstracts met the initial search criteria. Sixteen articles which met the predefined eligibility criteria were included in the final analysis. Overall, 1067 patients (out of them 723 men) with liver cirrhosis were evaluated for left ventricle diastolic dysfunction. In our systemic analysis we have found that 51.2% of cirrhotic patients had left ventricle diastolic dysfunction diagnosed and the grade 1 was the most prevalent (59.2%, P < 0.001) among them, the grade 3 had been rarely diagnosed - only 5.1%. The data about the prevalence of diastolic dysfunction in cirrhotic patients depending on Child-Pugh Classes was available from 5 studies (365 patients overall) and only in 1 research diastolic dysfunction was found being associated with severity of liver cirrhosis (P < 0.005). We established that diastolic dysfunction was diagnosed in 44.6% of Child-Pugh A class patients, in 62% of Child B class and in 63.3% of Child C patients (P = 0.028). The proportion of patients with higher diastolic dysfunction grades increases in more severe cirrhosis presentation (P < 0.001). There was no difference between mean MELD scores in patients with and without diastolic dysfunction and in different diastolic dysfunction groups. In all studies diastolic dysfunction was more frequent in patients with ascites. CONCLUSION: This systemic analysis suggests that left ventricle diastolic dysfunction is an attribute of liver cirrhosis which has not received sufficient attention from clinicians so far. Future suggestions of a comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients and give hint for better understanding of the left ventricle diastolic dysfunction pathogenesis in liver cirrhosis.

Impact of the Uridine⁻Cytidine Kinase Like-1 Protein and IL28B rs12979860 and rs8099917 SNPs on the Development of Hepatocellular Carcinoma in Cirrhotic Chronic Hepatitis C Patients-A Pilot Study.

Background and objectives: The hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma (HCC) in the western world. The efficacy of surveillance programs for early detection of HCC is not satisfactory: many tumors are diagnosed at the late, incurable stages. Therefore, there is a need in reliable prognostic markers for the proper follow-up of HCV-positive patients. The aim of the present study was to assess the prognostic value of the uridine⁻cytidine kinase-like protein 1 (UCKL-1), a putative oncoprotein, together with genetically determined polymorphisms in the interleukin 28B (IL28B) gene (rs12979860, rs8099917) in the development of HCC in HCV-positive cirrhotic patients. Materials and Methods: We included 32 HCV cirrhotic patients, 21 (65.6%) of whom had HCC. The expression of UCKL-1 was assessed in liver tissue sections, using immunohistochemistry. For IL28B rs12979860 and rs8099917 genotype analysis, the corresponding genomic regions were amplified by polymerase chain reaction (PCR) with appropriate primers. Results: We have found that UCKL-1 expression was significantly increased in HCC (p = 0.003). The presence of rs8099917 TT single-nucleotide polymorphism (SNP) elevated the chances of HCC manifestation more than sevenfold (OR = 7.3, p = 0.0273). The presence of rs12979860 CC SNP also heightened HCC chances more than sevenfold (OR = 7.5, p = 0.0765). Moreover, in the HCC group, a combination of IL28B rs12979860 non-TT and rs8099917 TT genotypes was observed more often, compared with the non-HCC group. Other combinations of IL28B rs12979860 and rs8099917 SNIPs were associated with a reduced risk of HCC development, approximately at the same extent. Conclusions: The presence of IL28B rs8099917 TT and rs12979860 CC SNPs, but not the intensity of UCKL-1 expression, is strongly associated with increased chances of HCC development in HCV-positive cirrhotic patients.

Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers.

We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). The majority of vaccinees had detectable antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, 70% against CRF01_AE virus-infected cells (median titer 239) and 84% against CRF01_AE gp120-coated cells (median titer 499). A high proportion (74%) of vaccinees had IFN-γ ELISpot responses, 63% to Gag and 42% to Env, 3 years after the second HIV-MVA boost. After the third HIV-MVA, there was an increase in Env-binding antibodies and ADCC-mediating antibodies relative to the response seen at the time of the third HIV-MVA vaccination, p < .0001 and p < .05, respectively. The frequency of IFN-γ ELISpot responses increased to 95% against Gag or Env and 90% to both Gag and Env, p = .064 and p = .002, respectively. In conclusion, the HIV-DNA prime/HIV-MVA boost regimen elicited potent antibody and cellular immune responses with remarkable durability, and a third HIV-MVA immunization significantly boosted both antibody and cellular immune responses relative to the levels detected at the time of the third HIV-MVA, but not to higher levels than after the second HIV-MVA.

Concise review of current concepts on nomenclature and pathophysiology of hepatic encephalopathy.

Hepatic encephalopathy is a neuropsychiatric complication of liver cirrhosis the symptoms of which may vary from imperceptible to severe, invaliding, and even lethal. Minimal hepatic encephalopathy is also important because of its tendency to impair patients' cognitive functions and quality of life. The polyetiological pathogenesis of hepatic encephalopathy is intensively studied. A general consensus exists that not only excess of ammonia but also inflammatory, oxidative, and other processes are significant in the development of hepatic encephalopathy.

Metabolic changes one year after laparoscopic adjustable gastric banding operation in morbidly obese subjects.

INTRODUCTION: Laparoscopic adjustable gastric banding (LAGB) is effective for weight reduction in severely obese patients. However, the data about its effect on metabolic syndrome (MS) are limited. AIM: To assess weight loss and changes of metabolic parameters 1 year after LAGB in a prospective, nonrandomized single center cohort study in morbidly obese subjects. MATERIAL AND METHODS: Physical examination, body weight (BW) parameters and metabolic profile were assessed at baseline and 1 year after LAGB in morbidly obese subjects. The incidence of MS was evaluated according to National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: One year after the operation data from 90 patients out of 103 were available. Mean excess weight (EW) loss of 33.1% was associated with a significant improvement in all metabolic parameters: decrease of hypertension by 15.8%, hypertriglyceridemia by 42.6%, and hyperglycemia by 46.3%; and increase in high density lipoprotein cholesterol by 48.3%. This resulted in the resolution of MS in 44.2% of subjects. The significant change in the distribution of MS components was observed with the highest frequency of 4 components before and 2 components after surgery. Patients with MS at baseline lost 29.9% of EW compared to 44.3% in those without MS (p = 0.009). CONCLUSIONS: The LAGB resulted in effective reduction of BW parameters in morbidly obese subjects 1 year after the operation. Along with the weight loss, resolution of MS and a significant shift towards decrease in the number of MS components was observed. Patients with MS were more resistant to the weight loss.

Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.

To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.

Anti-HCV prevalence in the general population of Lithuania.

BACKGROUND: The aim of this study was to assess risk factors for HCV acquisition and prevalence of anti-HCV in the general population of Lithuania. MATERIAL/METHODS: The study enrolled 1528 randomly selected adults from the 5 biggest cities of Lithuania and its rural regions. Screening for anti-HCV was performed by analysis of peripheral capillary blood with lateral flow immunochromatography and confirmation of positive cases by peripheral venous blood testing with 2-step chemiluminescent microparticle immunoassay. RESULTS: Anti-HCV prevalence in Lithuania is 2.78% and according to the standard European population the adjusted anti-HCV rate is 2.85%. It is more prevalent among men (crude rates: 4.02% males vs. 1.49% females, p=.0030) and this does not depend on age. Vilnius and Kaunas regions have higher infection rates than smaller rural regions (2.92% and 3.01% vs. 2.24%, 0.74% and 1.35%). Nowadays among our population HCV infection spreads mainly via intravenous drug use (OR=42.5, p<.0001). HCV transmission occurs through blood transfusions (OR=6.4, p=.0002), tooth removal (OR=4.1, p=.0048), childbirth (OR=5.0, p=.0224), multiple and a long-term hospitalization (OR=3.0, p=.0064), tattooing (OR=4.4, p=.0013), open traumas (OR=3.7, p=.0009) and intrafamilially (OR=11.3, p=.0002). CONCLUSIONS: 2.78% of the population is anti-HCV-positive. The anti-HCV rate is higher in Vilnius and Kaunas in comparison with other regions. HCV spreads mainly through intravenous drug use, but intrafamilial and some nosocomial routes are also important. The anti-HCV prevalence did not depend on age. Despite active prevention of nosocomial HCV transmission, the incidence of HCV infection does not decrease due to virus spread mostly in "trusted networks" of intravenous drug users.

Expression of cytokeratin 7 as a histological marker of cholestasis and stages of primary biliary cirrhosis.

UNLABELLED: The aim of this study was to estimate cytokeratin 7 (CK-7) expression in biopsy specimens of patients with different stages of primary biliary cirrhosis and clinicopathological patterns (cholestatic and hepatitic) and its correlation with some biochemical and pathological parameters and to examine a diagnostic value of CK-7 expression. MATERIAL AND METHODS: A total of 82 biopsy specimens of patients with primary biliary cirrhosis were analyzed. CK-7 expression was graded by 4 grades depending on the extent into parenchymal areas and bile duct epithelium. The correlations of CK-7 expression grade with copper deposition, bile duct/portal tract ratio, bilirubin concentration, and activity of alkaline phosphatase and gamma-glutamyl transpeptidase were studied. CK-7 expression was evaluated as a marker of cholestasis (cholestatic pattern) and inflammation (hepatitic pattern). RESULTS: A positive correlation of CK-7 expression grade with copper-binding protein grade (r=0.698, P<0.0001; OR=6.199, P<0.0001), serum bilirubin level (r=0.375, P=0.001), and alkaline phosphatase activity (r=0.276, p=0.014) was found. CK-7 expression grades correlated positively with histological stages of primary biliary cirrhosis (r=0.639, P<0.000) and negatively with granulomas (r=-0.432, P<0.0001; OR=0.173, P=0.0011). CONCLUSIONS: CK-7 expression is a sensitive marker of bile duct injury, which correlated well with histological stages of primary biliary cirrhosis, copper deposits, and biochemical markers of cholestasis: serum bilirubin level and alkaline phosphatase activity. Evaluation of CK-7 expression may improve the diagnosis of this serious and progressive disease. It is recommended to evaluate copper staining together with cytokeratin 7 expression in liver biopsy specimens for more precise diagnostic evaluation of asymptomatic primary biliary cirrhosis.

Changes in hepatitis C virus infection routes and genotype distribution in a Lithuanian cohort with chronic hepatitis C.

BACKGROUND: We evaluated the distribution of hepatitis C virus genotypes and determined their association with routes of infection according to the sex and age of the study subjects. MATERIAL/METHODS: We studied 1158 patients with chronic hepatitis C. Hepatitis C virus antibodies were detected with a microparticle enzyme immunoassay, hepatitis C virus ribonucleic acid was identified via polymerase chain reaction, and hepatitis C virus genotypes were determined with a line probe assay. An anonymous questionnaire completed by all subjects included the date of chronic hepatitis C diagnosis, the age and sex of the patient, the hepatitis C virus genotype and subtype, and possible routes of infection. RESULTS: Of the patients studied, 50.9% had more than 1 possible route of infection, 41.2% had a single route of infection, and 7.9% had an unknown route of infection. The most common hepatitis C transmission routes were intravenous drug use and tattoos in younger patients and surgery or long or multiple hospitalizations in older patients. The genotype distribution was as follows: genotype 1, 65.0% of patients; genotype 2, 26.3%; and genotype 3, 8.7%. The transmission of genotype 1 was associated primarily with surgery and that of genotype 3 was linked with intravenous drug use. CONCLUSIONS: Today, the main routes of hepatitis C virus transmission are intravenous drug use and tattoos. Some hepatitis C infections are associated with surgery or are acquired from a family member. The shift in transmission pathways predetermined the shift in hepatitis C virus genotypes from 1 to 3.

Primary biliary cirrhosis in Lithuania: diagnosis and clinical picture.

BACKGROUND: The rising detection and considerable geographical variation of primary biliary cirrhosis (PBC) in some regions demand increased awareness of the disease. The aim was to analyze the clinical, biochemical, immunological, and histological criteria of PBC patients in Lithuania and evaluate the patterns of disease presentation and histological features. MATERIAL/METHODS: One hundred thirty-one PBC patients were examined and followed in the Center of Hepatology, Gastroenterology, and Dietetics, Vilnius University Hospital. Their case records were evaluated in this retrospective record-review study. RESULTS: Most of the patients were women (94.6%) older than 50 years with late stages of PBC. Men were significantly older and had a threefold shorter duration from disease presentation to diagnosis (4.0+/-0.4 vs. 1.4+/-0.4 years). 29.8% of patients had asymptomatic disease at presentation and at diagnosis, were older than the symptomatic ones, and presented with significantly lower prevalence of jaundice, skin signs, and lower alkaline phosphatase (ALP) activity, but higher frequency of sicca syndrome. Antimitochondrial antibody (AMA) positivity was found in 91.7%, bile duct lesions in all patients, while the frequency of histological signs of cholestasis (except copper accumulation) was lower. No significant differences in these parameters in asymptomatic and symptomatic patients were found. CONCLUSIONS: Most PBC patients in Lithuania were at late histological stages, with a predominance of females older than 50 years and long duration from disease presentation to diagnosis. One third of these PBC patients initially had asymptomatic course, with some differences in clinical signs and their prevalence compared with initially symptomatic patients.